Reply to |[lsquo]|Lack of association of the heparanase gene single-nucleotide polymorphism Arg307Lys with acute lymphoblastic leukemia in patients from Northern Ireland|[rsquo]| by Winter et al.

The letter by Winter et al.1 presented a study of lack of association between rs11099592 single-nucleotide polymorphism (SNP) of the heparanase (HPSE) gene and acute lymphoblastic leukemia (ALL) in North Irish patients (22=2.866, P=0.26 for genotype comparison and 12=2.629, P=0.105 for allele comparison). These values could be an index of a trend toward ALL association. However, Winter et al.1 observed higher G allele frequency (83.63%) in North Irish ALL patients compared with their normal individuals (55.56%), whereas in our investigation,2 we found the prevalence of allele A in Israeli ALL patients (27.91%) compared with Israeli healthy individuals (16.51%). This A allele prevalence was also confirmed by the following haplotype analysis performed for five SNPs (rs4693608, rs11099592, rs4364254, rs6856901, rs4693602) in the HPSE gene. We may suggest that the absence of consensus in the two reports may be the results of the differences between the two studied populations. For example, many studies reveal no correlation between C3435T multidrug-resistance gene 1 (MDR1) polymorphism and MDR1 expression, especially between Caucasians and Japanese.3, 4 It is possible that certain haplotypes are more prevalent in one population than another. It is clear that only a large study with precise determination of subgroups and with appropriate control individuals may allow in the future to clarify the role of heparanase gene in ALL development. In addition, only future studies will detect the role of HPSE gene SNPs (as functional polymorphisms or as a marker) in expression and function of heparanase, and their involvement in various pathological processes. In their letter, Winter et al.1 tried to combine our two studies that were based on different samples. The aim of our first study was to characterize the HPSE gene SNPs in four Jewish populations and to compare them to non-Jewish populations.5 The ethnic origin of each individual was established by the origin of both maternal and paternal grandparents. In our second study,2 we investigated the association of HPSE gene SNPs with hematological malignancies. In this study, our patients group was heterogeneous, representing various Israeli ethnic populations (not only Ashkenazi, North Africans, Mediterranean and Near Eastern Jews, but also Yemenite, Ethiopian and other Jews and non-Jewish individuals). For this reason, we chose our 103 control individuals, randomly from the same Israeli population. Thus, the attempt of Winter and co-workers to compare these two different studies leads to incorrect conclusions.